The invention provides a process for the preparation of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol with a high stereoselectivity for the trans form from the enantiomers (1R,2R)- and (1S,2S)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol.
Tramadol, which is called “trans isomer” for historical reasons and comprises the trans form from the enantiomers (1R,2R)- and (1S,2S)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, has an analgesic action and is therefore employed as an analgesic.
As is known, 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol can be prepared by a Grignard reaction of 2-[(dimethylamino)methyl]cyclohexanone and the Grignard compound of 3-bromoanisole. Both the cis and the trans form are formed in this reaction.
The trans form, hereinafter referred to as the trans isomer, comprises the R,R and S,S enantiomers with the following two formulas:
The cis form, called cis isomer in the following, comprises the S,R and R,S isomers with the following two formulas:

In the preparation of tramadol with the aid of a Grignard reaction, a highest possible yield of the trans isomer, the tramadol Grignard base, is aimed for. In this regard, it is already known that the choice of solvents and/or presence of salt additives can influence the diastereoselectivity of the Grignard reaction.
According to the teaching of WO99/61405, a shift in the trans:cis isomer ratio from approx. 80:20 to 90:10 in the preparation of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol by the use of amine or ethers is described. However, the yield achieved is in some cases only comparable to a reaction without additions, and in some cases even significantly poorer.
Savelyev et al. (International Conference on Natural Products and Physiologically Active Substances, Novosibirsk, 30 Nov.–6 Dec. 1998, poster) also describe an increase in the diastereoselectivity in the preparation of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol by addition of dioxanes, but the total yield of cis and trans isomer of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol is adversely affected.